The major objective of this research proposal is to study regulation of the synthesis, storage and secretion of parathyroid hormone in the glands of animals and man both in vitro and in vivo in physiologic studies. The laboratory has worked extensively in protein chemistry and in the regulation of hormone secretion. The methods involved will close the gap between studies of isolated cells and perifused tissues in vitro systems and physiologic responses in animals and patients with transplanted parathyroid glands. The proposals include the development of new antibodies to portions of bovine, human and canine parathyroid hormone and proparathyroid hormone molecules, development of immunoprecipitation methods for studying prohormone synthesis and the use of the tools of molecular biology to work with the glands and cells in vitro. A unique opportunity to extrapolate the results of in vitro findings to animal and human physiology has been provided by the demonstrated success of the investigators in performing animal and human parathyroid transplantion. In a live dog transplant system, most of the observations which have been made in vitro in the past can be validated, expanded or refuted, providing an opportunity for close correlation of in vitro and in vivo findings. Furthermore, a unique opportunity for the study of man has been provided by the therapeutic transplantation of parathyroid glands into the forearm of patients with primary hyperplasia or renal failure with secondary hyperparathyroidism. When possible, clinical studies will be done in these patients to study the regulation of human hormone secretion. Intact parathyroid hormone rather than fragments is found in the effluent blood of the antecubital vein from patients with transplanted glands, providing the unique opportunity to study human parathyroid physiology.